Recently it has been shown that the C-terminus fragment of the tetanus toxin (Hc-TeTx) is transported retrogradely and had shown neuroprotective effects, preventing neuronal death by apoptosis. This could be a new alternative preventing ongoing cell death and restoring the motor function in Parkinson's disease (PD), which is characterized by dopaminergic neurodegeneration. Our aim was to evaluate the effects of local administration of Hc-TeTx on motor behavior and the dopamine (DA) levels in the striatum of MPP(+)-treated rats. In the rotational behavior task, the Hc-TeTx [2 microM]+MPP(+) group had a decreased number of contralateral rotations and the cylinder test improved for both forelimb-use asymmetry compared to the MPP(+) group. The staircase test showed that the Hc-TeTx+MPP(+) group had an improvement of fine motor skills compared to the same limb performance of the MPP(+) group. The group of animals with Hc-TeTx+MPP(+) had higher DA and metabolite levels compared to the MPP(+) group. Our study clearly shows that Hc-TeTx improves different motor behavior strongly, which favors the hypothesis of the Hc-TeTx fragment enhancing survival pathways that result in amelioration of the dopaminergic system of rats with a dopaminergic lesion.